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Biomedical subjects

A G Kleber

Publications and source records attributed to A G Kleber.

10 recordsLinked to original sources
PubMed1999

Genetic and molecular basis of cardiac arrhythmias: impact on clinical management parts I and II.

Genetic approaches have succeeded in defining the molecular basis of an increasing array of heart diseases, such as hypertrophic cardiomyopathy and the long-QT syndromes, associated with serious arrhythmias. Importantly, the way in which this new knowledge can be applied to managing patients and to the development of syndrome-specific antiarrhythmic strategies is evolving rapidly because of these recent advances. In addition, the extent to which new knowledge represents a purely research tool versus the extent to which it can be applied clinically is also evolving. The present article represents a consensus report of a meeting of the European Working Group on Arrhythmias. The current state of the art of the molecular and genetic basis of inherited arrhythmias is first reviewed, followed by practical advice on the role of genetic testing in these and other syndromes and the way in which new findings have influenced current understanding of the molecular and biophysical basis of arrhythmogenesis.

Arrhythmias, Cardiac↗
PubMed1997

Molecular and cellular aspects of re-entrant arrhythmias.

In recent years it has become evident that myocardial tissue undergoes remodeling in diseased states such as myocardial infarction and hypertrophy which affects membrane channels, cell-to-cell coupling as well as the connective tissue matrix. Although the detailed mechanisms of ventricular arrhythmias in ventricular hypertrophy are not known, studies carried out by computer simulations or high resolution mapping of electrical activity have suggested a complex interaction between changing ionic currents at the level of the cell membranes, altered cell-to-cell coupling and altered macroscopie-structure. The present report summarises these recent developments and their potential relevance for arrhythmogenesis.

Animals↗
PubMed1992

[Elevation of the ST-segment in the electrocardiogram and ischemic injury current].

The TQ segment depression and the ST segment elevation in the electrocardiogram during acute myocardial ischemia are caused by flow of injury current. This current flows between potential gradients across the ischemic border. The initial change is the TQ segment depression, which is brought about by a positive shift of the resting membrane potential of the ischemic cells. After 1 to 2 minutes ST segment elevation develops as a consequence of the action potential shortening and loss of plateau. The loss of potassium ions and ensuing extracellular K+ accumulation is the major cause of the alterations in action potential. After 15 to 20 minutes of ischemia, electrical cell-to-cell uncoupling occurs and interrupts the flow of injury current (decrease of TQ segment depression and ST segment elevation), producing conduction block.

Action Potentials↗
PubMed1986

Electrophysiological basis for arrhythmias caused by acute ischemia. Role of the subendocardium.

The major electrophysiological changes during the first 10 min of myocardial ischemia caused by complete obstruction of a coronary artery are a reduction in membrane potential, a decrease in action potential amplitude and upstroke velocity, and a prolongation of recovery of excitability following an action potential. Conduction velocity in the direction parallel to the long axis of myocardial fibers (VL) and in the transverse direction (VT) in normal myocardium are in the order of 40 cm/s and 20 cm/s respectively. During ischemia, conduction velocity decreases and lowest values for VL are in the order of 20 cm/s, for VT around 10 cm/s, before the ischemic tissue becomes inexcitable. Calculated dimensions of a possible re-entrant circuit in acutely ischemic myocardium (the product of refractory period and conduction velocity) are in the order of 7 to 8 cm. Re-entrant circuits of such dimensions were indeed demonstrated by simultaneous recording of 125 extracellular potentials from the epicardial surface of the ventricles during spontaneously occurring ventricular arrhythmias after coronary occlusion. Previous studies provided evidence that premature ventricular depolarization which initiate re-entry originated in the subendocardium, and the present experiments confirmed this. Destruction of the subendocardium of isolated, Langendorff perfused canine hearts, including the Purkinje system, by intracavitary application of phenol, did not, however, abolish ectopic activity during either ischemia or reperfusion, although the nature of the arrhythmias during ischemia was different from those in intact hearts. Coupling intervals of ectopic beats were longer in phenol-treated hearts than in intact hearts, but the site of origin of initial ectopic beats leading to ventricular tachycardia could not be determined. Re-entrant circuits with revolution times in the order of 340 to 400 ms accounted for the slow tachycardias observed in phenol-treated hearts. In contrast to intact hearts, these tachycardias never degenerated into ventricular fibrillation, indicating that an intact Purkinje system may be a necessary requirement for ventricular fibrillation to occur during acute, regional myocardial ischemia.

Animals↗